Pneumonia is the leading cause of death from nosocomial infections. Intubation and mechanical ventilation greatly increase the risk of bacterial ventilator-associated pneumonia (VAP). Growth of potentially pathogenic bacteria in dental plaque of critically ill patients provides a nidus of infection for microorganisms that have been shown to be responsible for the development of VAP. Since these organisms are concentrated in dental plaque, removal of organisms form the oral cavity by oral care interventions is a theoretically attractive method to reduce the risk of development of VAP. However, evidence-based protocols for oral care of mechanically ventilated patients are not available. Thus, we propose a prospective, randomized clinical trial to test the effects of three oral care interventions (mechanical, MECHI; pharmacologic, PHARMI; and combination, mechanical plus pharmacologic, COMBI) in reducing the risk of developing VAP. The primary aim of this study is to test the effects of mechanical, pharmacologic and combination (mechanical plus pharmacologic) oral care interventions on dental plaque, oral microbial flora and oral immunity in critically ill mechanically ventilated adults. Secondary aims are to1) examine the effects of mechanical, pharmacologic and combination (mechanical plus pharmacologic) oral care interventions on development of VAP in critically ill mechanically ventilated adults; and 2) describe any differential effects of mechanical and pharmacologic oral care interventions on the development of VAP in specific patient populations (medical, surgical, and neurologic critically ill patients). A total of 456 subjects will be randomly assigned to 4 groups (control, MECHI, PHARMI, COMBI) in order to attain an adequate sample size of 300 subjects. The effects of interventions will be examined using a between-subjects 22 factorial design. A two-factor analysis of variance will be used to conduct significance tests, including tests of the effect of each intervention (MECHI, PHARMI, and COMBI) on the outcomes of dental plaque (UM-OHI score), oral immunity (salivary IgA and lactoferrin), oral flora (semi-quantitative culture), and development of VAP (CPIS score). Results of the study have the potential to positively affect patient well-being, morbidity, mortality and health care costs.